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α-Diazo homophotalimides were reacted with various propiolic acids on Rh 2 (esp) 2 catalysis. The resulting propiolate esters were transformed into novel, heterocyclic Δ α,β -spirobutenolides in good to excellent product yields. The approach represents a fundamentally novel entry into natural-like Δ α,β -spirobutenolides present in many biologically active natural products as well as fully synthetic compounds endowed with diverse biological activities. The Δ α,β -spirobutenolides thus obtained were shown to inhibit thioredoxin reductase, a selenocysteine enzyme target for cancer. Moreover, for the best compound in the series (TrxR IC 50 1.49 ± 0.08 μM), it was shown, using MALDI-TOF mass-spectrometry, that it selectively binds selenocysteine in the presence of a 10-fold excess of cysteine. This validates the new compound as a promising lead for anticancer therapy development.

New types of cyclic diazo compounds capable of Rh(II)-catalyzed spirocyclizations with tetrahydrofuran have been discovered. The formation of the spirocyclic framework is thought to proceed via the...

Attempted use of 3-arylglutaconic acids in the three-component version of the Castagnoli-Cushman reaction with amines and aromatic aldehydes resulted in an unexpected formation of 4,6-diaryl 1,6-dihydropyridine-2(3 H)-ones. These are of interest as representatives of a rare heterocyclic chemotype for de novo biological investigation. Alternatively, these compounds can be oxidized into their 2-pyridone counterparts, stereoselectively reduced to give cis-configured 4,6-diaryl 2-piperidones, or isomerized to 5,6-dihydropyridin-2(1 H)-ones. All the three scaffolds are well represented in the bioactive compound domain.

The first example of the Castagnoli-Cushman reaction of homophthalic acid with an amine and an aldehyde conducted in a three-component format is reported. This new protocol employs no dehydrating agents and, unlike the traditional Castagnoli-Cushman reaction of homophthalic anhydride, allows simultaneous mixing of all three reagents and provides good to excellent yields of trans-configured tetrahydroisoquinolonic acids.

The aim of this review is to present the entire range of cyclooctynes that are currently known in the literature. We provide a generalized and systematic overview of methods for their synthesis and consider the applications of cyclooctynes for the purposes of molecular biology and cellular engineering. The importance of cyclooctynes for [3+2] azide-alkyne cycloaddition is demonstrated, as the high reactivity of cyclooctynes allows to perform this reaction under mild conditions without a catalyst.

A new format for the Castagnoli–Cushman reaction of structurally diverse dicarboxylic acids, amines, and aldehydes in the presence of acetic anhydride as dehydrating agent is described. The reaction is distinctly amenable to parallel format: the combinatorial array of 180 reactions delivered 157 products of >85% purity without chromatographic purification (of this number, 143 compounds had >94% purity). The new method offers a convenient preparation of the skeletally and peripherally diverse, lead- and druglike γ- and δ-lactam carboxylic acids with high diastereoselectivity in combinatorial fashion.

Literature examples illustrating the use of oxalyl chloride to prepare dicarboxylic acid anhydrides are surprisingly limited. At the same time, we have discovered a method involving the use of this readily available reagent which allowed the preparation of novel cyclic anhydrides where other, more conventional, methods had failed. Herein, we demonstrate that the method is applicable to a wide diversity of substrates, delivers good to excellent yields of cyclic anhydrides without chromatographic purification and can be considered a synthetic tool of choice whenever dicarboxylic acid cyclodehydration is required.

A novel protocol for the Castagnoli–Cushman reaction of dicarboxylic acids and imines comprises the use of 1,1′-carbonyldiimidazole as the cyclodehydrating agent to in situ produce the intermediate anhydrides. In contrast to previously developed procedure involving the use of acetic anhydride, the current protocol allows one to utilize substrates prone to acylation or acid-promoted transformations, which significantly broadens the reaction scope of lactams to be obtained.

Spirocyclic motifs are emerging privileged structures for drug discovery. They are also omnipresent in the natural products domain. However, until today, no attempt to analyze the structural diversity of various spirocyclic motifs occurring in natural products and their relative populations with unique compounds reported in the literature has been undertaken. This review aims to fill that void and analyze the diversity of structurally unique natural products containing spirocyclic moieties of various sizes.